Method of making catheters with porous structure for carrying additional agents

ABSTRACT

A method of making catheters is disclosed in which the wall of the catheter has a porous structure for carrying additional agents, such as therapeutic or diagnostic agents. The method includes providing a core, applying a base polymer material and an inert material over the outer surface of the core, and consolidating the base polymer material to form a catheter having a porous polymer layer with the inert material contained within the pores thereof. The inert material can be applied with the base polymer material, or it can be applied in a separate step after the base polymer material has been partially consolidated to form the porous polymer layer. Additional agents can be mixed with the inert material before it is applied to the catheter, or such agents can be applied to the porous polymer layer of the catheter in a separate step after the inert material is removed therefrom.

RELATED APPLICATIONS

This application is a continuation-in-part of U.S. patent applicationSer. No. 11/234,514 filed on Sep. 22, 2005, which claims priority ofU.S. Provisional Application No. 60/612,673 filed on Sep. 22, 2004. Thecontent of these prior applications are incorporated herein byreference.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates generally to methods of manufacturingmedical tubing. In particular, the present invention relates to methodsof making catheters having a porous structure in which additives, suchas therapeutic or diagnostic agents, can be carried.

2. Description of the Related Art

Medical tubing and catheters are widely employed for a variety oftreatment and diagnostic procedures involving, for example, theadministration of fluid medications and devices into a patient and theremoval of fluids from the patient. In this application, the terms“catheter” and “medical tubing” will be used interchangeably to refer tothe same structure.

The ultimate use for which medical tubing is designed requires that thetubing have certain physical characteristics. For example, a cathetermust be sufficiently stiff or rigid to enable its insertion and movementthrough narrow body orifices and channels and, in some applications,must also be able to withstand a high bursting pressure. On the otherhand, a catheter must be sufficiently soft and flexible so that it mayreadily conform to body shapes so as not to cause injury to the interiorwall of a patient's vessel as it is advanced. In addition, a cathetermust be of sufficient mechanical strength to resist tearing duringnormal use, such as when the catheter is removed against tissueresistance.

In many medical devices, the polymer used to construct these devices isfirst compounded with additional agents, such as coloring agents,plastisizers, and opacifiers to obtain optimum properties of the medicaldevice for which the polymer is used. Such compounding generallyinvolves adding the desired additive to pellets of the polymer andrunning the mix through a compounder (e.g., an extruder) where thepolymer is sheared apart and inherently blends with the polymer. Aftermanufacturing, the devices are often coated with things to reducefriction, improve blood compatibility, or provide therapeutic benefits.Such surface coatings are difficult to accomplish because the surfacemust be prepared correctly and the coatings are often rubbed or wornoff.

The Applicant previously developed a method for nonextrusionmanufacturing of catheters, which is described in U.S. Pat. No.6,030,371. In this existing method, a catheter is formed by spraying afine polymer particulate, or solvenated polymer particulate, over a coreto form a polymer shell of the catheter. The polymer material can bevaried over the length of the catheter by using different hardnesspolymers to gradually vary the hardness of the catheter. The '371 patentteaches that the different hardness polymers can be colored to providevisual confirmation of the transition of hardness. The '371 patent alsoteaches the application of an opacifier material with the polymermaterial, or between layers of the polymer material. The polymer andopacifier materials are consolidated, for example, by heating in anoven.

Existing catheter manufacturing methods have not recognized thesignificant advantages that can be obtained by developing a catheterhaving a porous structure that can be used to carry therapeutic agents,diagnostic agents, and/or other desired agents into a patient's body.

SUMMARY OF THE INVENTION

The present invention provides a method of making catheters in which theside wall of the catheter has a porous structure for carrying additionalagents, such as therapeutic or diagnostic agents. The method includesproviding a core having an outer surface, applying a base polymermaterial and an inert material, such as silicone, over the outer surfaceof the core, and consolidating the base polymer material to form acatheter having a porous polymer layer with the inert material containedwithin the pores of the porous polymer layer. The inert material, whichcan be a liquid or a solid, can be applied with the base polymermaterial, or the inert material can be applied in a separate step afterthe base polymer material has been partially consolidated to form theporous polymer layer. Additional agents, such as therapeutic and/ordiagnostic agents, can be mixed with the inert material before the inertmaterial is applied to the catheter, or such agents can be applied tothe porous polymer layer of the catheter in a separate step after theinert material is removed from the pores thereof.

According to a broad aspect of the present invention, a method of makinga catheter is provided, comprising the steps of: providing a core havingan outer surface; applying a base polymer material and an inert materialover a length of the outer surface of the core; and consolidating thebase polymer material to form a catheter having a porous polymer layerwith inert material contained within the pores thereof.

According to another broad aspect of the present invention, a method ofmaking catheters is provided, comprising the steps of: providing a corehaving an outer surface; applying a nonextruded layer of base polymermaterial over a length of the outer surface of the core; partiallyconsolidating the base polymer material; filling voids left in thepartially consolidated base polymer material with an inert material; andcompleting the consolidation of the base polymer material with the inertmaterial in the voids to thereby form a catheter having a porous polymerlayer with inert material contained within the pores thereof.

According to another broad aspect of the present invention, a method ofmaking catheters is provided, comprising the steps of: providing a corehaving an outer surface; applying a nonextruded layer of a slurrycontaining a base polymer material and an inert material over a lengthof the outer surface of the core; and consolidating the base polymermaterial within the slurry to thereby form a catheter having a porouspolymer layer with inert material contained within the pores thereof.

Numerous other objects and features of the present invention will beapparent to those skilled in this art from the following descriptionwherein there is shown and described exemplary embodiments of thepresent invention, simply by way of illustration of the modes bestsuited to carry out the invention. As will be realized, the invention iscapable of other different embodiments, and its several details arecapable of modification in various obvious aspects without departingfrom the invention. Accordingly, the drawings and description should beregarded as illustrative in nature and not restrictive.

BRIEF DESCRIPTION OF THE DRAWINGS

The present invention will become more clearly appreciated as thedisclosure of the present invention is made with reference to theaccompanying drawings. In the drawings:

FIG. 1 shows a core mandrel over which a catheter will be constructedaccording to the present invention.

FIG. 2 shows a liner placed over the mandrel in the cathetermanufacturing process of the present invention.

FIG. 3 shows a filament winding operation for applying a filament overthe mandrel and liner in the catheter manufacturing process of thepresent invention.

FIG. 4 shows a plurality of base polymer materials and an opacifiermaterial being applied over the filament winding according to thecatheter manufacturing process of the present invention.

FIG. 5 shows a process step of heating the base polymer material topartially consolidate the material.

FIG. 6 shows a process step of applying an inert material over thepartially consolidated base polymer material.

FIG. 7 shows a process step of heating the base polymer material tocompletely consolidate the base polymer material with the inert materialcontained therein.

FIG. 8 shows a process step of washing the inert material from the basepolymer material using a solvent to create a porous polymer layer.

FIG. 9 shows a process step of applying an additional agent, such as atherapeutic or diagnostic agent, to the porous polymer layer.

FIG. 10 is a process flow chart showing a series of process steps formaking a catheter according to one embodiment of the present invention.

FIG. 11 is a process flow chart showing a series of process steps formaking a catheter according to another embodiment of the presentinvention.

FIG. 12 is a process flow chart showing a series of process steps formaking a catheter according to another embodiment of the presentinvention.

FIG. 13 is a process flow chart showing a series of process steps formaking a catheter according to another embodiment of the presentinvention.

DETAILED DESCRIPTION OF THE INVENTION

A method of making a catheter with a porous structure for carryingadditional agents according to the present invention will now bedescribed in detail with reference to FIGS. 1 to 13 of the drawings.

The method of making a catheter starts with a core mandrel 10, as shownin FIG. 1. The catheter will be constructed over the core mandrel 10using much of the same technology disclosed in the Applicant's priorU.S. Pat. No. 6,030,371, which is incorporated herein by reference.

A catheter liner 12 is placed over the core mandrel 10, as shown in FIG.2. The liner 12 can be formed of a variety of different materials, butis generally less than 20% of the intended wall thickness. As anexample, a liner having a 0.00150 inch wall thickness of TFE can beused. Alternatively, the process of the present invention can beperformed without a liner, whereby a polymer material is applieddirectly on the mandrel 10.

A reinforcement filament is then applied over the liner 12, as shown inFIG. 3. During this operation, the mandrel/liner combination is loadedinto rotating chucks 14. A filament winding head 16 travels on a screwcarrier 18 longitudinally along the mandrel 10 to apply fibrousreinforcement filament 20 over the mandrel at a winding angle range of 0to 90 degrees relative to the longitudinal axis of the catheter. Forportions of the catheter that require great circumferential rigidity orkink resistance, a very tight winding angle (e.g., 80 to 90 degrees) ofthe reinforcement filament 20 can be used, and for portions of thecatheter that require low rigidity, the reinforcement filament 20 can beapplied in a low winding angle (e.g., 0 to 10 degrees). The windingangle of the reinforcement fiber 20 can be continuously varied over thelength of the catheter by controlling the rotation speed of the mandrel10 and the movement of the filament winding head 16 along the support18.

At either the same time or after the reinforcement filament is applied,an atomizing spray head 22 traverses the mandrel/liner, as shown in FIG.4. The spray head 22 applies an atomized spray that fuses to thesubstrate surface the sprays impinge upon (i.e., the mandrel 10, theliner 12, the reinforcement fiber 20, or the previous layer of polymermaterial). The substrate can be preheated to ensure complete fusion ofthe sprayed polymer to the substrate. This preheating can beaccomplished with infrared, hot air, or resistance heating of the coremandrel 10 or other suitable means.

A suitable atomizing spray head 22 according to the present invention isdescribed in detail in the Applicant's prior U.S. Pat. No. 6,030,371.The atomizing spray head 22 is connected to one or more containers 30and 31 of polymer materials having varying degrees of hardness or otherdesired properties. The atomizing spray head 22 can also be connected toa container 32 of an opacifier material, such as tungsten.

While the mandrel/liner is spinning, the atomizing spray head 22traverses along a path parallel to the axis of the rotatingmandrel/liner. As it traverses this path, a metering valve (not shown)can be set such that only the harder polymer (e.g., from the container30) is applied at what will be the proximal end of the catheter. As thehead 22 traverses the mandrel/liner, the metering valve is controlledsuch that it ports to the harder polymer to a lesser degree and to thesofter polymer (e.g., from the container 31) to a higher degree untilfinally only the softest polymer is applied at the distal tip of thecatheter, which will serve as the soft distal tip of the catheter. Thedifferent hardness polymer materials used in the present invention canbe colored to provide visual confirmation of the transition of hardness.

In a similar fashion, opacifying powder can be selectively applied fromthe container 32. In one example, a single layer of polymer material canbe applied as the filaments are placed. The single layer of polymermaterial can be followed by a layer of opacifier material and anotherlayer of polymer material. A significant benefit of applying opacifierin this manner is that the movement of the head 22 can be pausedmomentarily to apply circumferential rings of high opacifierconcentration, which serve as markers when the catheter is used underX-ray.

The present invention also includes process steps that create a porousstructure in the catheter wall for carrying additional agents, such astherapeutic or diagnostic agents. These process steps will be describedwith reference to FIGS. 5 to 9 of the drawings.

In FIG. 5, the base polymer coated member 12 is heated by a heat source34 to a sufficient temperature and for a sufficient time to partiallyconsolidate the base polymer material. The heat is removed before thebase polymer material is fully consolidated. When the heat is removed,the partially consolidated polymer material solidifies and creates acatheter body formed by sections that have melted and sections that havenot melted. The partially consolidated polymer material has voids formedtherein into which a liquid material can be wicked or otherwise infused.

In FIG. 6, an inert material 33, such as liquid silicone, is sprayedonto the outer surface of the partially consolidated base polymermaterial using a spray head 24. An inert material in liquid form canalso be applied to the partially consolidated base polymer material bybrushing or dipping or other known methods. The inert material wicks orotherwise infuses into the voids left by the partially consolidated basepolymer material. The inert material can be either a liquid, such asliquid silicone, or a solid, such as a salt, and is selected frommaterials that will not bond with the base polymer material when thebase polymer material is consolidated. This allows the inert material tobe removed from the base polymer material later in the process, asexplained below.

In FIG. 7, the base polymer coated member 12 is again heated by a heatsource 34 to a sufficient temperature and for a sufficient time tocompletely consolidate the base polymer material with the inert materialin the voids thereof. A catheter structure is thereby formed having aporous polymer layer with an inert material contained within the poresthereof.

In FIG. 8, a solvent 35 is used to wash out the inert material from thepores of the catheter structure. Once the inert material is washed out,the catheter structure has a porous polymer layer with true voids formedin the polymer layer. The voids in the polymer layer can be filled withan additional agent, as explained below.

In FIG. 9, an additional agent 36, such as a therapeutic agent or adiagnostic agent, is applied to the porous polymer layer. The additionalagent 36 can be applied by spraying with a spray head 37, as shown inFIG. 9, or it can be applied by dipping, brushing, or other methods thatallow the additional agent to be wicked or otherwise infused into theporous polymer.

The process described above and shown in FIGS. 5 to 9 provides acatheter having an additional agent, such as a therapeutic and/ordiagnostic agent, carried in a porous structure on the outer surface ofthe catheter. The process of creating the porous structure using aninert material allows the additional agent to be added after the hightemperature consolidation process for the polymer has been completed.Thus, additional agents that cannot withstand high temperatures can beeffectively added to and carried by the catheter using the process ofthe present invention. A flow chart of the process steps according tothis embodiment of the present invention is provided in FIG. 10.

In another embodiment, an inert material can be mixed with the polymermaterial and applied with the polymer material in the process step shownin FIG. 4. The polymer material can then be completely consolidated byheating, as shown by the process step in FIG. 7 (in this case, thepartial consolidation step shown in FIG. 5 and the separate step ofapplying inert material shown in FIG. 6 can both be eliminated). Thecatheter formed by the consolidated base polymer material with inertmaterial contained therein can then be washed in solvent to remove theinert material, as shown by the process step of FIG. 8, thereby forminga catheter structure having a porous polymer layer. An additional agentcan then be applied to the porous polymer layer, as shown by the processstep of FIG. 9. A flow chart of the process steps according to thisembodiment of the present invention is provided in FIG. 11.

For additional agents that can withstand high temperatures, an inertmaterial, such as silicone, can be used as a carrier for the agent (theagent is mixed in). In this case, the same process as described abovecan be used, except that the inert material would not have to be washedout. For example, the inert material with an agent mixed in could beapplied in the process step shown in FIG. 6, and the catheter would befinished upon completing the consolidation step shown in FIG. 7. A flowchart of the process steps according to this embodiment of the presentinvention is provided in FIG. 12.

In another embodiment, the inert material and additional agent can bothbe mixed in with the base polymer material and applied to the outersurface of the core together in the process step shown in FIG. 4. Inthis case, the process steps shown in FIGS. 5, 6, 8 and 9 could beeliminated, and the catheter would be finished upon completing theconsolidation step shown in FIG. 7. A flow chart of the process stepsaccording to this embodiment of the present invention is provided inFIG. 13.

After the base polymer material is completely consolidated, the cathetercan be rough-sized by passing a cutter over the surface of the catheterand then polished. The catheter body can then be removed from therotating chucks 14 and is ready for finishing operations, such ascurving or hubbing.

In the embodiments described above, the consolidation is accomplished byheating. However, it is contemplated that in some cases consolidationcan be better accomplished by other known techniques, such as drivingoff solvent from a solution.

The additional agent(s) used in the present invention can be therapeuticagents such as anticoagulants, anti-inflamatories, oxides, and genetherapy materials, and/or diagnostic agents.

While the invention has been specifically described in connection withspecific embodiments thereof, it is to be understood that this is by wayof illustration and not of limitation, and the scope of the appendedclaims should be construed as broadly as the prior art will permit.

1. A method of making a catheter, comprising the steps of: providing acore having an outer surface; applying a nonextruded layer of basepolymer material over a length of said outer surface of the core;partially consolidating the base polymer material; filling voids left inthe partially consolidated base polymer material with an inert material;and completing the consolidation of the base polymer material with theinert material in the voids to thereby form a catheter having a porouspolymer layer with inert material contained within the pores thereof. 2.The method according to claim 1, wherein the inert material is a liquid.3. The method according to claim 1, wherein the inert material is asolid.
 4. The method according to claim 1, wherein the inert material issilicone.
 5. The method according to claim 1, wherein said step ofpartially consolidating the base polymer material comprises heating theapplied base polymer material for a sufficient time and temperature tocause only part of the base polymer material to consolidate, and thenremoving the heat therefrom so that said layer of base polymer materialhas portions that have consolidated and portions that have notconsolidated.
 6. The method according to claim 1, wherein said step offilling voids left in the partially consolidated base polymer materialcomprises spraying the inert material over the partially consolidatedbase polymer material.
 7. The method according to claim 1, wherein saidstep of filling voids left in the partially consolidated base polymermaterial comprises brushing an inert fluid over the partiallyconsolidated base polymer material.
 8. The method according to claim 1,wherein said step of filling voids left in the partially consolidatedbase polymer material comprises dipping the partially consolidated basepolymer material into an inert fluid.
 9. The method according to claim1, further comprising the step of removing the inert material from thepores of the porous polymer layer.
 10. The method according to claim 9,further comprising the step of filling the pores of the porous polymerlayer with an additional agent after removing the inert materialtherefrom.
 11. The method according to claim 10, wherein said additionalagent is a therapeutic or diagnostic agent.
 12. The method according toclaim 1, wherein said step of filling voids left in the partiallyconsolidated base polymer material comprises filling the voids with aninert material having an additional agent mixed therein.
 13. The methodaccording to claim 12, wherein said additional agent is a therapeutic ordiagnostic agent.
 14. A method of making a catheter, comprising thesteps of: providing a core having an outer surface; applying anonextruded layer of a slurry containing a base polymer material and aninert material over a length of said outer surface of the core; andconsolidating the base polymer material within the slurry to therebyform a catheter having a porous polymer layer with inert materialcontained within the pores thereof.
 15. The method according to claim14, wherein said slurry is applied by spraying on the outer surface ofthe core.
 16. The method according to claim 14, wherein base polymermaterial is consolidated by applying heat to the nonextruded layer. 17.The method according to claim 14, further comprising the step ofremoving the inert material from the pores of the porous polymer layer.18. The method according to claim 17, further comprising the step offilling the pores of the porous polymer layer with an additional agentafter removing the inert material therefrom.
 19. The method according toclaim 18, wherein said additional agent is a therapeutic or diagnosticagent.
 20. The method according to claim 14, wherein said slurrycontains an additional agent mixed with the inert material, which willremain in the pores of the porous polymer layer after the base polymermaterial is consolidated.
 21. The method according to claim 20, whereinsaid additional agent is a therapeutic or diagnostic agent.
 22. A methodof making a catheter, comprising the steps of: providing a core havingan outer surface; applying a base polymer material and an inert materialover a length of said outer surface of the core; and consolidating thebase polymer material to form a catheter having a porous polymer layerwith inert material contained within the pores thereof.